title: The cAMP effector EPAC activates Elk1 transcription factor in prostate smooth muscle, and is a minor regulator of α1-adrenergic contraction.
abstract: BACKGROUND
  Prostate smooth muscle tone is regulated by α1-adrenoceptor-induced contraction and cAMP-mediated relaxation. EPAC is an effector of cAMP, being involved in smooth muscle relaxation and cell cycle control outside the lower urinary tract. Here, we investigated the expression and function of EPAC in human prostate tissues from patients undergoing radical prostatectomy.
  
  
  RESULTS
  mRNA and protein expression of EPAC was detected in all prostate tissues by RT-PCR and Western blot analysis. Immunoreactivity was observed in stromal cells, and colocalized with immunofluorescence for α-smooth muscle actin and calponin. Under normal conditions, noradrenaline- or phenylephrine-induced contraction of prostate strips in the organ bath was not affected by the EPAC activator pCPT (SP-8-pCPT-2'-O-Me-cAMPS.NA) (30 μM). However, when the cyclooxygenase inhibitor indomethacin (50 μM) was added, EPAC activators pCPT and OME (8-CPT-2'-O-Me-cAMP.Na) (30 μM) significantly reduced contractions by low concentrations of phenylephrine. These effects were not observed on noradrenaline-induced contraction. OME and pCPT caused phosphorylation of the transcription factor Elk1 in prostate tissues. Elk1 activation was confirmed by EMSA (electrophoretic mobility shift assay), where OME and pCPT incresed Elk1 binding to a specific DNA probe.
  
  
  CONCLUSIONS
  EPAC activation may reduce α1-adrenergic prostate contraction in the human prostate, although this effect is masked by cyclooxygenases and β-adrenoceptors. A main EPAC function in the human prostate may be the regulation of the transcription factor Elk1.
authors.affiliation: Department of Urology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hennenberg
authors.forename: Frank
authors.initials: F
authors.lastname: Strittmatter
authors.forename: Henning
authors.initials: H
authors.lastname: Schmetkamp
authors.forename: Beata
authors.initials: B
authors.lastname: Rutz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction; D014551:Urinary Tract / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism*
chemical_list: C494112:ELK1 protein, human; D018340:Receptors, Adrenergic, alpha-1; D050807:ets-Domain Protein Elk-1; D004917:Erythromycin; C057513:erythromycin propionate-N-acetylcysteinate; D000111:Acetylcysteine